C.Cg-Tg(DO11.10)10Dlo/J

Stock number: 003303
Product name: DO11.10
Research areas: Immunology, Inflammation and Autoimmunity Research, Research Tools

Description

Mice carrying this MHC class II restricted rearranged T cell receptor transgene on a H2d background react to ovalbumin (OVA) peptide antigen. Intraperitoneal administration of OVA to transgenic mice results in a rapid deletion of the immature CD4+ CD8+ TCRlo thymocytes with progression to mature thymocytes. Apoptosis of cortical thymocytes in these mice occurs within 20 hours of treatment. These mice may be useful for studies of T cell selection and death in immune responses and in the generation of tolerance, as well as for studying the mechanisms of apoptosis.

Detailed description

Mice carrying the MHC class II restricted rearranged T cell receptor transgene, Tg(DO11.10)10Dlo, react to ovalbumin (OVA) peptide antigen. Intraperitoneal administration of OVA to transgenic mice results in a rapid deletion of the immature CD4⁺ CD8⁺ TCR^lo thymocytes with progression to mature thymocytes. Apoptosis of cortical thymocytes within 20 hours of treatment indicates that apoptosis in important in the development of antigen-induced tolerance. Use of this rearranged T cell receptor transgene requires H2^d background.

Of note, the DO11 transgene with the C57BL/6-associated Thy1.1 (Thy1^a) allele is available as Stock No. 036332 C.Cg-Thy1^a Tg(DO11.10)10Dlo/AkhoAbhmJ.

Development

Constructs, about 45 to 50 kilobases, made from full genomic TCR rearranged genes from the DO11.10 hybridoma of Kappler and Marrack were co-microinjected into (B6C3F1) female X BALB male embryos by Dr. Ken Murphy in the laboratory of Dr. Dennis Loh at Washington University, St. Louis in 1989. Founder mice were bred back to BALB/c repeatedly. The Tg(DO11.10)10Dlo transgene contains rearranged Tcra and Tcrb genes and is expressed in the majority of T cells. These rearranged transgenes encode a chicken ovalbumin-specific MHC class II (I-A^d)-restricted T cell receptor. The alpha chain has the V-alpha 13 sequence and the beta chain has the V-beta 8.2 sequence (see Blackman et al., Cell 47:349-357). Two copies of the alpha chain and four copies of the beta chain appear to have co-integrated in Chromosome 18 near D18MIT144 (see Gorham et al. 1996; PMID:8901605 ). Although the cosmid backbone was excised before microinjection, this transgene insertion includes the neomycin resistance cassette.

Allele

Symbol: Tg(DO11.10)10Dlo
Name: transgene insertion 10, Dennis Y Loh
MGI accession ID: MGI:2664398
Generation method: Transgenic
Attributes: Inserted expressed sequence
Marker symbol: Tg(DO11.10)10Dlo
Marker name: transgene insertion 10, Dennis Y Loh
Chromosome: 18
Strain of origin: (C57BL/6 x C3H)F1 x BALB/c
Expressed genes: Tcra,T cell receptor alpha chain,mouse, laboratory; Tcrb,T cell receptor beta chain,mouse, laboratory
Site of expression: T cells
Molecular note: This double transgene contains rearranged Tcra and Tcrb genes and is expressed in the majority of T cells. These rearranged transgenes from the DO11.10 T cell hybridoma encode a chicken ovalbumin-specific MHC class II (I-A^d)-restricted T cell receptor. The allele was created by injection of a mix of the two separate transgenes Tg(TcraDO11.10)#Dlo and Tg(TcrbDO11.10)#Dlo into oocytes.
General note:

Mice carrying this pair of MHC class II restricted rearranged Tcra and Tcrb T cell receptor transgenes on a H2^d background react to ovalbumin (OVA) peptide antigen. Intraperitoneal administration of OVA to transgenic mice results in a rapid deletion of the immature CD4⁺ CD8⁺ TCR^lo thymocytes with progression to mature thymocytes. Apoptosis of cortical thymocytes in these mice occurs within 20 hours of treatment.